Bending the HIV epidemic curve: can prevention cascades show us how?
Authors: Rashida A Ferrand, Katharina Kranzer
Journal: The Lancet Global Health (2023)

Progress in reducing HIV infections in the first decade of the 21st century has faltered over the past 5 years. An estimated 1·5 million new HIV infections occurred globally in 2021, 1 million more than the global targets.1UNAIDSIn Danger: UNAIDS Global AIDS Update 2022.https://www.unaids.org/en/resources/documents/2022/in-danger-global-aids-updateDate: 2022Date accessed: April 15, 2023Google Scholar The range of HIV prevention tools at our disposal has increased over the past decade, but maximising their effect and bending the epidemic curve remains a challenge. In The Lancet Global Health, Michael Pickles and colleagues2Pickles M Gregson S Moorhouse L et al.Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling study.Lancet Glob Health. 2023; 11: e1105-e1113Summary Full Text Full Text PDF Google Scholar use the HIV prevention cascade framework to model the number of new HIV infections that would be averted in eastern Zimbabwe over the next 10 years if existing barriers to correct and consistent use of three preventive interventions (tenofovir-based oral pre-exposure prophylaxis [PrEP], voluntary medical male circumcision [VMMC], and condoms) were overcome.3Schaefer R Gregson S Fearon E Hensen B Hallett TB Hargreaves JR HIV prevention cascades: a unifying framework to replicate the successes of treatment cascades.Lancet HIV. 2019; 6: e60-e66Summary Full Text Full Text PDF PubMed Scopus (45) Google Scholar The cascade framework encompasses three steps, namely motivation, access, and capacity to use effectively, each with multiple barriers. The median effect of mitigating barriers to each step for all three prevention methods in all priority populations, with plausible interventions, is 12 200 averted HIV infections of the 28 500 total expected infections in people aged 15–54 years. The definition of priority populations is broad and essentially includes all sexually active individuals aged 15–54 years, with additional specifications for PrEP (HIV negatives only with casual partners) and VMMC (men only). However, these priority populations do not necessarily wholly constitute those in need of HIV prevention because people move in and out of at-risk situations, and this movement can be affected by a variety of demographic, interpersonal, and psychosocial factors.4Auerbach JD Gerritsen AA Dallabetta G Morrison M Garnett GP A tale of two cascades: promoting a standardized tool for monitoring progress in HIV prevention.J Int AIDS Soc. 2020; 23e25498Google Scholar Addressing all cascade steps in one priority population was shown to be more effective than addressing one step across all populations. However, focusing on one cascade step, such as motivation, across multiple preventive interventions might create synergies and be more cost-effective than addressing all steps for individual interventions. According to the framework, reasons for not being motivated include knowledge, risk perception, consequences of use, and social norms. All these reasons could be addressed for multiple prevention methods, ideally during HIV testing and counselling, which is often the gateway to accessing preventive services. Pickles and colleagues2Pickles M Gregson S Moorhouse L et al.Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling study.Lancet Glob Health. 2023; 11: e1105-e1113Summary Full Text Full Text PDF Google Scholar highlight that PrEP has the most difficult barriers to overcome across each cascade step; hence, removing those barriers would result in the greatest number of avertable HIV infections. However, there are valid reasons why correct and consistent use of PrEP has faced considerable challenges in implementation and uptake.5Ahmed N Pike C Bekker LG Scaling up pre-exposure prophylaxis in sub-Saharan Africa.Curr Opin Infect Dis. 2019; 32: 24-30Crossref PubMed Scopus (25) Google Scholar Effective use in the Manicaland cohort (which provided data for the study by Pickles and colleagues2Pickles M Gregson S Moorhouse L et al.Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling study.Lancet Glob Health. 2023; 11: e1105-e1113Summary Full Text Full Text PDF Google Scholar) is defined as somebody answering yes to the question: “Are you currently taking PrEP?” The proportion of people answering affirmatively was less than 1%, suggesting very low coverage as seen in many other settings.6Hensen B Floyd S Phiri MM et al.The impact of community-based, peer-led sexual and reproductive health services on knowledge of HIV status among adolescents and young people aged 15 to 24 in Lusaka, Zambia: the Yathu Yathu cluster-randomised trial.PLoS Med. 2023; 20e1004203Crossref Scopus (0) Google Scholar, 7Sila J Larsen AM Kinuthia J et al.High awareness, yet low uptake, of pre-exposure prophylaxis among adolescent girls and young women within family planning clinics in Kenya.AIDS Patient Care STDS. 2020; 34: 336-343Crossref PubMed Scopus (19) Google Scholar By contrast to VMMC, effective PrEP use relies on medication adherence and persistence, which is not taken into account in the model. Although adherence might be high in trial settings (>80% of adolescent girls and young women in South Africa had detectable tenofovir diphosphate levels in their blood at 3 and 6 months post PrEP initiation),8Celum C Hosek S Tsholwana M et al.PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: results from HPTN 082, a randomized controlled trial.PLoS Med. 2021; 18e1003670Crossref PubMed Scopus (47) Google Scholar it is very different in practice. A recent study from Kenya reported that less than 10% of people (1908 of 25 542) who had initiated PrEP returned for the refill after 3 months.9Were D Musau A Mutegi J et al.Using a HIV prevention cascade for identifying missed opportunities in PrEP delivery in Kenya: results from a programmatic surveillance study.J Int AIDS Soc. 2020; 23e25537Google Scholar High attrition was seen across all risk populations, including female sex workers and men who have sex with men, despite high HIV infection risk. Even in those who continue to engage with PrEP services, low adherence has been reported.10Tapsoba JD Cover J Obong'o C et al.Continued attendance in a PrEP program despite low adherence and non-protective drug levels among adolescent girls and young women in Kenya: results from a prospective cohort study.PLoS Med. 2022; 19e1004097Crossref Scopus (2) Google Scholar Removing all barriers across all steps of the cascade for PrEP for sexually active HIV-negative women aged 25–54 years with a casual partner would result in 20% of them taking PrEP and avert 8·4% of all HIV infections. The proportion of the total population assumed to fall into the priority population for PrEP is not reported by Pickles and colleagues,2Pickles M Gregson S Moorhouse L et al.Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling study.Lancet Glob Health. 2023; 11: e1105-e1113Summary Full Text Full Text PDF Google Scholar but is likely to be considerable. Hence, removing all barriers for PrEP would result in a substantial number of people receiving medication in addition to the 1 200 000 people receiving antiretroviral therapy for treatment of their HIV infection in Zimbabwe. Although there are populations that will undoubtedly benefit from PrEP, it is questionable whether providing PrEP to such a high number is or should be the priority for a resource-constrained country, such as Zimbabwe. PrEP requires continued engagement and adequate adherence, which is resource-intensive. By contrast, VMMC is a one-off intervention, and condoms are already well established and do not require any continuous interaction with an under-resourced health-care system. The feasibility of these prevention methods has been well established over at least a decade, and therefore, they should be prioritised. We declare no competing interests. Strengthening the HIV prevention cascade to maximise epidemiological impact in eastern Zimbabwe: a modelling studyInterventions exist in eastern Zimbabwe to reduce HIV towards elimination, but barriers of motivation, access, and effective use prevent their full effect being realised. Interventions need to be multilayered and address all steps along the HIV prevention cascade. Models incorporating the HIV prevention cascade can help to identify the main barriers to greater effectiveness. Full-Text PDF Open Access